More than 100 million dental restorations are performed each year with more than half of those presently being filled using composite restorative materials. Despite this scale of usage and implementation, the composite restorative is often not a lifelong restoration of either function or appearance. Secondary caries, mechanical failure and various other failure mechanisms are responsible for reducing the useful lifetime of many restorations. Further, the bioavailability and degradation of monomers that are extracted from conventional composites has been implicated in several adverse phenomena, including reduced immune function, changes to the microbial distribution in the oral environment, and the acceleration of growth of bacteria involved in the evolution of biofilms and additional secondary cavities that result in reduced service lifetimes.
Currently, most commercial photocurable dental restorative resins are based on dimethacrylates and the reaction mechanism is through chain-growth free radical polymerization. Existing dimethacrylate systems are popular for fillings and other dental prostheses because of their esthetic merit and “cure-on-command” feature. These formulations have resulted in significant advancements in the field of dentistry. Such dental restorative materials are often mixed with 45 to 85% by weight (wt %) silanized filler compounds such as barium, strontium, zirconia silicate and/or amorphous silica to match the color and opacity to a particular use or tooth.
Although easy to use, these dimethacrylate systems have several drawbacks and there are a number of properties of the resin chemistry that, if improved upon, would increase the performance, longevity and biocompatibility of composite restorations (Sakaguchi et al., 2005, Dent. Mat. 21:43-46; Dauvillier et al., 2001, J. Biomed. Mat. Res. 58(1):16-26, 2001; Dauvillier et al., 2000, J. Dent. Res. 79(3):818-823; Yourtee et al., 1997, In Vitro Tox. 10:245-251). The most significant shortcomings of methacrylate-based resins are high volumetric shrinkage (Ferracane, 2005, Dent. Mat. 21:36-42), high polymerization stress (Braga et al., 2005, Dent. Mat. 21:962-970; Lu et al., 2005, Dent. Mat., 21(12):1129-1136; Braga and Ferracane, 2002, J. Den.1 Res. 81:114-118) and low functional group conversion (Darmani and Al-Hiyasat, 2006, Dent. Mat. 22:353-358; Sasaki et al., 2005, J. Mat. Sci.: Mat. Med. 16:297-300; Pulgar et al., 2000, Envir. Health Persp. 108:21-27). The chain growth polymerization mechanism results in long chains and therefore early gelation which contributes to both volume shrinkage and shrinkage stress. The current systems typically only reach a final double bond conversion of 55-75%, which not only contributes to the insufficient wear resistance and mechanical properties, but also jeopardizes the biocompatibility of the composites due to the leachable unreacted monomers. Additionally, the residual monomer left in the restoration after curing is extractable and reactive due to its ester functionalities (inherent to methacrylates), and may leach out of the restoration and into the body, with unknown consequences (Sasaki et al., 2005, J. Mat. Sci.: Mat. Med. 16:297-300; Pulgar et al., 2000, Envir. Health Persp. 108:21-27). There is concern that residual monomers may cause allergic reactions and sensitization in patients (Theilig et al., 2000, J. Biomed. Mat. Res. 53(6):632-639). There is also reason to believe that release of the most common reactive diluent, triethylene glycol dimethacrylate (TEGDMA), may also contribute to local and systemic adverse effects by dental composites (Hansel et al., 1998, J. Dent. Res. 77(1):60-67; Englemann et al., 2001, J. Dent. Res. 80(3):869-875; Schweikl and Schmalz, 1999, Mut. Res.-Gen. Toxic. Envir. Mutag. 438:71-78; Darmani and Al-Hiyasat, 2006, Dent. Mat. 22:353-358).
Upon polymerization, shrinkage stresses transferred to the tooth can cause deformation of the cusp or enamel microcracks (Davidson and Feilzer, 1997, J. Dent. Res. 25:435-440; Suliman et al., 1993, J. Dent. Res. 72(11):1532-1536; Suliman et al., 1993, J. Dent. Res. 9(1):6-10), and stress at the tooth-composite interface may cause adhesive failure, initiation of microleakage and recurrent caries. In addition, significant increases in volumetric shrinkage and shrinkage stress are experienced when the double bond conversion is increased to reduce the leachable monomer (Lu et al., 2004, J. Biomed. Mat. Res. Part B—Applied Biomat. 71B:206-213). This trade-off of conversion and shrinkage has been an inherent problem with composite restorative materials since their inception.
Nucleophilic reactions of thiols to several functional groups such as electron deficient vinyls (i.e., thiol-Michael addition reaction), isocyanates and epoxides are known to proceed extremely efficiently under mild conditions, with no by-products at room temperature, minimal amounts of catalysts like a base, high functional group tolerance and high conversions, and thus widely considered as “click” reaction (Hoyle et al., 2010, Chem. Soc. Rev. 39:1355-1387; Hoyle & Bowman, 2010, Angew. Chem. Int. Ed. 49:1540-1573; Lowe, 2010, Polym. Chem. 1:17-36). The thiol-X reaction family has been used in organic synthesis, polymer formation, and materials modification in recent decades (Hoyle et al., 2004, J. Polym. Sci., Part A: Polym. Chem. 42:5301-5338; Hoyle et al., 2010, Chem. Soc. Rev. 39:1355-1387; Hoyle & Bowman, 2010, Angew. Chem., Int. Ed. 49:1540-1573; Lowe, 2010, Polym. Chem. 1:17-36) Given that the versatile thiol-click chemistry can be used to synthesize highly functional materials under relatively facile reaction conditions, various thiol-vinyl reaction qualify as highly efficient click reactions as used in applications that range from complex dendrimer synthesis (Killops et al., 2008, J. Am. Chem. Soc. 130:5062-50645), convergent synthesis of star polymers (Chan et al., 2008, Chem. Commun. 40:4959-4961), functional biodegradable lactides (Nuttelman et al., 2008, Prog. Polym. Sci. 33:167-179) to surface modifications of films (Khire et al., 2007, Macromolecules 40:5669-5677) and nanoparticles (Khire et al., 2008, J. Polym. Sci., Part A: Polym. Chem. 46:6896-69069). One of the most powerful aspects of the thiol-vinyl reaction family is that it can be mediated by various species such as radicals (i.e., the classical thiol-ene reaction), acids, bases, nucleophiles and highly polar solvents. Each of these reaction pathways exhibits some or all of the characteristic advantages of the thiol-vinyl reaction.
A base or nucleophile mediated thiol reaction, often referred to as the thiol-Michael addition reaction, has attracted great interest for its high reactivity with relatively low amount of catalysts and its orthogonality to radical mediated reactions. Among several catalysts that are used for the thiol-Michael addition reaction, nucleophiles such as organophosphines (Chan et al., 2010, Macromolecules 43:6381-6388) and nucleophilic tertiary amines (Xi et al., 2012, ACS Macro Lett. 1:811-814) are known to be efficient catalysts for the thiol-Michael addition reaction. An activated vinyl, also referred to as an electron deficient vinyl, is suitable for thiol-Michael addition reactions since it accelerates the nucleophilic attack of a thiolate anion on a vinyl (Mather et al., 2006, Prog. Polym. Sci. 31:487-531). Carbonyl conjugated vinyls, such as acrylates and maleimides are well known as activated vinyls for Michael addition. Vinyl sulfone, a sulfone conjugated vinyl, is a functional group that has a highly electron deficient vinyl and has been used extensively as a textile dye since the 1950's (U.S. Pat. No. 2,657,205). The vinyl sulfone group is highly reactive towards the hydroxyl groups of the cellulose present in textile fibers under alkaline conditions. Additionally, the thiol-Michael addition product of vinyl sulfone forms a very stable thioether sulfone bond (Mather et al., 2006, Prog. Polym. Sci. 31:487-531; Morales-Sanfrutos et al., 2010, Org. Biomol. Chem. 8:667-675), while the counterparts of acrylates and maleimides contain relatively labile thioether ester or succinimide bonds (Schoenmakers et al., 2004, J. Controlled Release 95:291-300; Rydholm et al., 2007, Acta Biomater. 3:449-455).
There is a need in the art to develop novel monomer systems that afford useful composites systems once polymerized. Such composite systems should have superior chemical and physical properties, allowing for their use in challenging applications, such as dental restorations. The present invention fulfills these needs.